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Both functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) have been used to non-invasively localize the human motor functional area. These locations can be clinically used as stimulation target of TMS treatment. However, it has been reported that the finger tapping fMRI activation and TMS hotspot were not well-overlapped. The aim of the current study was to measure the distance between the finger tapping fMRI activation and the TMS hotspot, and more importantly, to compare the network difference by using resting-state fMRI. Thirty healthy participants underwent resting-state fMRI, task fMRI, and then TMS hotspot localization. We found significant difference of locations between finger tapping fMRI activation and TMS hotspot. Specifically, the finger tapping fMRI activation was more lateral than the TMS hotspot in the premotor area. The fMRI activation peak and TMS hotspot were taken as seeds for resting-state functional connectivity analyses. Compared with TMS hotspot, finger tapping fMRI activation peak showed more intensive functional connectivity with, e.g., the bilateral premotor, insula, putamen, and right globus pallidus. The findings more intensive networks of finger tapping activation than TMS hotspot suggest that TMS treatment targeting on the fMRI activation area might result in more remote effects and would be more helpful for TMS treatment on movement disorders.

The structural differences between arteries and veins are genetically predetermined. Vascular identity markers, the molecular markers specific to veins and arteries, determine the differential development of vessels during embryogenesis and their expression persists in adult vessels. It is revealed that they can be reactivated under various pathophysiologic conditions even after vessel differentiation. Thus, once considered as quiescent in adults, vascular identity markers may actually play significant roles in vascular remodeling. Manipulation of vascular identity and the underlying molecular mechanisms might be a novel strategy to improve vascular remodeling for clinical application., (© 2020 S. Karger AG, Basel.)

Purpose: Several radiographic parameters describe humeral head coverage by the acromion. We describe a new radiographic measurement, the acromion-greater tuberosity impingement index (ATI), and its ability to predict rotator cuff pathology., Methods: The ATI was measured with magnetic resonance imaging (MRI) and X-ray analysis in 83 patients with rotator cuff pathology and 76 patients with acute rotator cuff tears. The lateral acromial angle (LAA), acromion type, the acromion index (AI) and the critical shoulder angle (CSA) were measured to assess their correlations with the ATI. Receiver operating characteristic (ROC) curves were used to predict degenerative rotator cuff pathology. The change in the ATI after acromion surgery was evaluated in both groups., Results: According to the ROC curves, the ATI is a good predictor of degenerative rotator cuff pathology on both X-ray (cut-off, 0.865) and MRI (cut-off, 0.965). Patients with degenerative rotator cuff pathology had a significantly higher average ATI compared to the trauma group ( p = 0.001 for X-ray and MRI). The degenerative group had a significantly lower LAA ( p = 0.001) and a higher ratio of type III acromion ( p = 0.035) than the trauma group. The ATI on X-ray was negatively related to the LAA and positively related to the AI, the CSA and acromion type (each p < 0.05). The ATI on MRI was negatively related to the LAA and positively related to the AI and acromion type (each p <0.05). More patients in the degenerative group than the trauma group needed acromioplasty or acromion decompression ( p < 0.05). The ATI on MRI was significantly lower after acromion surgery compared to before surgery in both groups ( p < 0.05)., Conclusion: The ATI is a good predictor of degenerative supraspinatus tendon tears or subacromial impingement syndrome. The ATI on MRI is more accurate and can precisely guide acromion surgery.

Unplanned surgery cancellation (USC) was an important quality management issue in the course of medical care for surgical patients, which caused inappropriate use of hospital resources and had negative impacts on quality and safety. This study used Lean Six Sigma to reduce the incidence of USC. Following the Lean Six Sigma DMAIC (Define, Measure, Analyze, Improve, and Control) process, the main factors influencing the USC were identified, such as the time of informing patient admission, the time of submitting operation notice, and the management of test report follow-up. A series of measures were implemented including improving the health education content of virtual bed patients, standardizing the way of communication between the Admission Management Center and the patients, improving the timing of anesthesia evaluation, optimizing the process of operation notice with an information system, and implementing the regulations of virtual bed management. The incidence of USC reduced from 10.21% in Jan. 2016 to 3.8% in Dec. 2016, and the Z -score increased from 1.25 to 1.68, which improved patient safety and demonstrated that Lean Six Sigma was an effective method to solve cross-department issues in hospital.

Objective To investigate the role of thioredoxin interacting protein(TXNIP)/ nucleotides-binding oligomerization domain-like receptor protein(NLRP)3 inflammasome in the sciatic nerve of streptozotocin(STZ)-induced diabetic rats. Methods The diabetic rat model was established by single intraperitoneal injection of STZ.The rats with matched sex and age were taken as normal control group.The blood glucose and body weight were monitored.The mechanical withdrawal threshold was measured by von Frey filaments at 12 weeks after the model was established.At 12 weeks,the rats were sacrificed and the sciatic nerves were separated for Luxol fast blue staining,the expressions of TXNIP,NLRP3,caspase-1,and interleukin(IL)-1β were detected by immunohistochemistry and Western blot method,and the levels of IL-1β and IL-18 in serum were measured by enzyme-linked immunosorbent assay(ELISA). Results The expression of TXNIP protein in the sciatic nerve of diabetic rats was 3.78±0.08,which significantly increased than that in the normal control group(0.99±0.06)( t =26.980, P <0.0001).Compared with the normal control group(0.97±0.05),the expression of NLRP3 protein in the diabetic group(2.44±0.16)was significantly higher( t =8.885, P <0.0001).The expression of cleaved caspase-1 was 4.45±0.19 in the diabetic group and 1.08±0.06 in the normal control group,and the difference was significant( t =16.900, P <0.0001).The expression of IL-1β protein in the diabetic group(4.50±0.16)was significantly higher than that(1.19±0.08)in the normal control group( t =18.630, P <0.0001).Compared with the normal control group,the levels of IL-1β [(110.50±8.80)pg/ml vs. (17.97±3.18)pg/ml, t =9.892, P <0.0001] and IL-18 [(591.70±8.78)pg/ml vs. (160.70±8.33)pg/ml, t =35.620, P <0.0001] in the serum of diabetic rats significantly increased. Conclusion The pathogenesis of diabetic peripheral neuropathy may be related to increased expression of TXNIP,activation of NLRP3 inflammasome,and downstream inflammation,which may provide a new target for diabetic peripheral neuropathy therapy.

Background: Pulmonary arterial hypertension (PAH) caused by congenital heart disease (CHD) is very common in clinics. Some studies have shown that PAH is related to the number of endothelial progenitor cells (EPCs), but there is no report on the relationship between PAH and the number of EPCs in children with CHD., Methods: In this study, a total of 173 cases with CHD (from 0 to 6 years old) were collected. According to the mean pulmonary arterial pressure (mPAP) measured by right heart catheterization, these cases were divided into PAH groups (including high PAH group, mPAP> 25 mmHg, n = 32, and the middle PAH group, 20 mmHg ≤ mPAP≤25 mmHg, n = 30) and non-PAH group (mPAP< 20 mmHg, n = 111). Peripheral blood was taken for flow cytometry, and the number of EPCs (CD133+/KDR+ cells) was counted. The number of EPCs /μL of peripheral blood was calculated using the following formula: EPCs /μL = WBC /L × lymphocytes % × EPCs % × 10 - 6 ., Results: The median EPCs of the non-PAH group, middle PAH group and high PAH group is 1.86/μL, 1.30 /μL and 0.98/μL, respectively. The mPAP decreases steadily as the level of EPCs increases (P < 0.05). After adjustment of gender, age and BMI, the number of EPCs was significantly associated with a decreased risk of high PAH (OR = 0.37, 95% CI: 0.16-0.87, P < 0.05). However, EPCs was not significantly associated with middle PAH (P > 0.05)., Conclusion: The findings revealed that the EPCs and high PAH in patients with CHD correlate significantly and EPCs may become an effective treatment for PAH in patients with CHD. EPCs may be a protective factor of high PAH for children with CHD.

To reveal the distribution characteristics of carbon, nitrogen and phosphorus in the sediments of Zhushan Bay at Taihu Lake, sedimentary columns were collected and sliced by 2 cm vertically from ten sampling points in three sections of Zhushan Bay. The content of total nitrogen (TN), total phosphorus (TP), and total organic carbon (TOC) were determined for each slice to reveal their horizontal and vertical distribution. The results showed that:spatially, the content of TN, TP, and TOC increased in the surface sediments of Zhushan Bay from the open lake area to the bay, and inside the bay these indexes were significantly higher than in the open lake area ( P <0.01). The content of TN, TP, and TOC in the surface sediments in the bay (section A) were 1.53 mg·g -1 , 1.55 mg·g -1 , and 11.31 mg·g -1 , respectively, while in the surface sediments near the open lake (section C) they were only 0.75 mg·g -1 , 0.57 mg·g -1 , and 6.70 mg·g -1 , respectively. Vertically, a feature of surficial enrichment was shown, and the contents of carbon, nitrogen and phosphorus in all three sections showed a decreasing trend with increase of depth. The contents of TN, TP and TOC in the surface sediments are 2-3 times, 2-5 times, and 2-3 times those in the bottom sediments, respectively. Generally, the average TP content in the sediment of Zhushan Bay is 0.93 mg·g -1 , suggesting an apparent heavy pollution, while the average TN content is 1.11 mg·g -1 as slight pollution. According to the organic nitrogen index and comprehensive pollution index, the northern part of Zhushan Bay is suffering from heavy pollution, where the organic pollution is relatively strong. The TP pollution index is between 1.03 and 3.87, indicating heavy pollution in Zhushan Bay.

Objective: To analyze the expression of CCR7 and Tim-3 in childhood patients with acute lymphoblastic leukemia (ALL) and their predictive value for prognosis., Methods: Eighty-six newly diagnosed ALL childhood patients from January 2007 to January 2017 treated in our hospital were selected. The expression level of CCR7 and Tim-3 in bone marrow isolated cells of ALL patients were detected by flow cytometry, all the patients were divided into the recurrence group and non-recurrence group according to the follow-up results, the differences in the expressions of CCR7, Tim-3 between the two groups were compared. The correlation between the expression of CCR7 , Tim-3 and the clinicopathologic features of ALL patients were analyzed, the predictive value of CCR7 and Tim-3 for the prognosis of newly ALL patients were evaluated by ROC curve, and the relationship between serum CCR7, Tim-3 and prognosis were analyzed., Results: The expression levels of CCR7 and Tim-3 in recurrence group were significantly higher than those in non-recurrence group(P<0.05). The critical value of CCR7 for diagnosis of recurrence was 45.97%, the sensitivity was 66.7%, the specificity was the 84.5% and the area under ROC curve (AUC) was 0.798 (95CI 0.777-0.939). The critical value of Tim-3 for diagnosis of recurrence was 53.54%, the sensitivity was 73.3%, the specificity was the 80.3% and the AUC was 0.806 (95CI 0.792-0.947). The AUC of the combined detection of CCR7 and Tim-3 was 0.895 (95CI 0.914-0.996), sensitivity 86.6%, specificity 78.9% (P<0.05); There was no significant correlation between CCR7, Tim-3 expression and age, sex, hemoglobin concentration, number of white blood cells, bone marrow blasts, platelets, central nervous system invasion, fusion gene (P>0.05). The exogenous infiltration rate of patients with high expression of CCR7 and Tim-3 was significantly higher than those in low expression group (P<005). The high expression rate 76.9% of Tim-3 in patients with T-ALL was significantly higher than that of B-ALL patients with Tim-3 high expression rate 45.2% (P<0.05). The median OS of patients with CCR7 level ≥45.97% and <45.97% were 9.3 months and 13.6 months respectively(P=0.004), and the Tim-3≥53.54% and Tim-3<53.54% were 9.1 months and 13.6 months respectively(P=0.001). The results of Cox's multi-factor regression analysis showed that CCR7 level(HR=1.024, 95 CI 1.001-1.049) and Tim-3 level (HR=1.879, 95 CI 1.183- 2.985) were the independent risk factors that affect the OS in ALL patients(P<0.05)., Conclusion: The expression of CCR7 and Tim-3 in bone marrow isolated cells of ALL patients shows good predictive value for prognosis, and the combination of CCR7 and Tim-3 can improve the sensitivity of the detection, the higher expression of CCR7 and Tim-3 can be used as potential indexes in prognosis evaluate.

The recession of regulatory T cells (Tregs) contributes to development of autoimmune disease. Our previous study suggested that prenatal nicotine exposure (PNE) inhibited Tregs frequency in offspring, but the mechanisms are still uncertain. This study aimed to explore the molecular mechanisms of PNE-induced Tregs inhibition from the perspective of cellular cholesterol homeostasis both in vivo and in vitro. PNE mice model were established by 3 mg/kg/d nicotine administration in Balb/c strain from gestational day (GD) 9 to GD 18. The results showed that PNE significantly decreased thymic Tregs frequency in neonatal offspring. The activation of mTOR and downregulation of p-STAT5/Foxp3 pathway of Tregs were observed in PNE offspring. Mechanism study found that PNE elevated ATP-binding cassette transporter G1 (ABCG1) expression and decreased intracellular cholesterol content of Tregs in offspring, indicating impaired intracellular cholesterol homeostasis. Similar results were observed in 1 μM nicotine-treated primary thymocytes in vitro. Further, cholesterol-replenishment can abrogate nicotine-induced mTOR activation and the following suppression of p-STAT5/Foxp3 pathway and Tregs frequency. In addition, Abcg1 siRNA transfection can partly reverse the nicotine-decreased intracellular cholesterol content and cell frequency of Tregs. In conclusion, this study showed that PNE could suppress Tregs development in female mice by up-regulating ABCG1-dependent cholesterol efflux, and suggested that PNE-induced thymic Tregs recession of offspring at early life was the developmental origin mechanism of immune dysfunction in later life., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Cross-project defect prediction (CPDP) aims to predict the defect proneness of target project with the defect data of source project. Existing CPDP methods are based on the assumption that source and target projects should have the same metrics. Heterogeneous cross-project defect prediction (HCPDP) builds a prediction model using heterogeneous source and target projects. Existing HCPDP methods just focus on one source project or multiple source projects with the same metrics. These methods limit the scope of getting the source project. In this paper, we propose Heterogeneous Defect Prediction with Multiple source projects (HDPM) which can use multiple heterogeneous source projects for defect prediction. HDPM based on transfer learning which can learn knowledge from one domain and use it to help with other domain. HDPM constructs a projective matrix between heterogeneous source and target projects to make the distributions of source and target projects similar. We conduct experiments on 14 projects from four public datasets and the results show that HDPM can achieve better performance compared with existing CPDP methods, and outperforms or is comparable to within-project defect prediction method. The use of multiple heterogeneous source projects for defect prediction can effectively extend the data acquisition range of defect prediction and make software defect prediction better applied to software engineering.

Background: To investigate the effects of levosimendan on right ventricular (RV) function in patients with acute decompensated heart failure (ADHF)., Methods: Patients with ADHF admitted from January 2017 to October 2017 were enrolled in this study. The patients were randomized to receive 24-h intravenous levosimendan or placebo. Echocardiographic examinations were performed and the parameters were compared. Epidemiological data were recorded and compared before and after treatment. Major adverse cardiac events during hospitalization and during 1-month follow-up were compared., Results: The baseline characteristics were comparable. After 24-h infusion of levosimendan and placebo, the left ventricular ejection fraction and S' were significantly increased in the levosimendan group compared with the control group (both p < 0.05). The E value in the levosimendan group significantly decreased (75.38 ± 8.32 vs. 88.21 ± 10.36, p < 0.0001), and E/e' significantly increased in the control group (19.61 ± 6.52 vs. 27.58 ± 8.22, p < 0.0001). The levels of right ventricular fractional area change (24 ± 3 vs. 20 ± 2, p < 0.0001) and tricuspid annular plane systolic excursion (1.56 ± 0.36 vs. 1.38 ± 0.21, p < 0.0001) were significantly higher in the levosimendan group than in the control group. After treatment, the values of systolic pulmonary artery pressure (SPAP) decreased in both groups (both p < 0.05), and the value of SPAP in the levosimendan group was lower than that in the control group (47.22 ± 5.6 vs. 55.85 ± 7.41, p < 0.0001). After 1-month follow-up, there was no significance in readmissions due to recurrent heart failure., Conclusions: Levosimendan seems to provide more beneficial effects among patients with ADHF to improve RV function, along with a decrease in pulmonary pressure.

The new phthalideisoquinoline hemiacetal alkaloids ( 2 - 7 ) and the known analogues ( 1 and 8 ) were isolated from the bulbs of Corydalis decumbens . The new compounds were characterized by analysis of their NMR spectroscopic data, chemical degradation syntheses, X-ray crystallography, and comparison of experimental and calculated ECD data. All the isolates were screened in vitro for inhibitory activity of spontaneous calcium oscillations in primary cultured neocortical neurons. Compounds 1 - 3 and 5 - 7 were found to be active in the suppression of spontaneous calcium oscillations with IC 50 values of 6.8, 5.6, 11.6, 10.2, 8.3, and 3.1 μM, respectively. It was also observed that the presence of hydroxy, methoxy, and ethoxy groups at the remote stereogenic center C-7' of some isolated phthalideisoquinoline hemiacetal alkaloids could alter the preferred conformation and invert the sign of optical rotation, rather than this resulting from configurational isomerism at C-1 or C-9, and that the 3 J 1,9 coupling constants of these analogues varied accordingly. For example, compounds 1 and 6 are levorotatory, despite these molecules having the same carbon skeleton and absolute configuration as (+)-egenine. This emphasizes the potential risk of incorrectly assigning absolute configuration based only on observed coupling constants or optical rotation when comparing the data of new compounds with literature values for known analogues, especially within this class of molecules.

The safety of a novel microbial muramidase (Muramidase 007) as a feed additive for swine was evaluated in a target animal safety study (Experiment 1). Forty weanling pigs were allotted to 4 dietary treatments: T1 control group, and 3 groups receiving Muramidase 007 in increasing doses: T2 65,000 (1X), T3 325,000 (5X) and T4 650,000 (10X) LSU(F)/kg feed. The efficacy of Muramidase 007 on growth performance was evaluated in a feeding experiment (Experiment 2). A total of 288 piglets were allotted to two groups: T1 control group and T2 receiving Muramidase 007 at 50,000 (LSU(F)/kg feed. In Experiment 1, no growth depression of pigs was observed. No adverse effects of Muramidase 007 were observed for any of the hematology and serum chemistry parameters measured or on pig health status. Post-mortem evaluation showed no adverse effects due to Muramidase 007 supplementation in the gross pathology or in the histological examination. In Experiment 2, Muramidase 007 significantly increased overall (d 0-42) average daily gain (ADG) and tended to improve overall average daily feed intake (ADFI) and day 42 body weight of nursery pigs and had no effect on feed conversion ratio (FCR). Overall, results of these studies show that there were no adverse effects of Muramidase 007 compared to the control group., (© 2019 The Authors.)

The recession of regulatory T cells (Tregs) is pivotal for type 1 diabetes (T1D) progressing. Our previous study observed the decreased Tregs in prenatal nicotine exposure (PNE) offspring, but whether this led to the onset of T1D remains uncertain. Thus, this study aimed to investigate the effects of PNE on T1D susceptibility and the role of PNE-suppressed Tregs in T1D of female offspring. The decreased body weights and elevated blood glucose levels from postnatal day (PND) 21 to PND 42 indicated that PNE caused persistent impaired glucose homeostasis in offspring. The elevated serum glutamic acid decarboxylase autoantibody, the "Gold Standard" for the detection of T1D, was observed on PND 42, suggesting the early stage of T1D in PNE offspring during adolescence. The reduced pancreatic islet areas and beta cells number in PNE offspring were observed at neonatal period and became more severe during adolescence. In addition, PNE caused immune dysfunction in offspring, manifested as suppressed thymic Tregs percentage from PND 4 to PND 42 and splenic Tregs/Th17 ratio on PND 42. In conclusion, PNE resulted in metabolic changes of offspring that were consistent with T1D characteristics, which could be the consequence of Tregs recession from early life to adolescence., (Copyright © 2019. Published by Elsevier B.V.)

In shallow eutrophic lakes, benthic bioclastic deposits accumulate abundant organic carbon derived from macrophyte detritus. Taking the typical macrophyte-dominated Xukou Bay as the study area, field investigations were performed using sediment cores to evaluate benthic phytodetritus accumulation. Specifically, nutrient contents, TOC/TN ratios, pigmentation, and biodegradable compounds were measured as descriptive parameters. The results show that the benthic bioclastic deposit had accumulated abundant pigments, nutrients, and biodegradable compounds derived from macrophytes detritus. These were mainly localized in the top 15 cm of sediments. Nitrogen loading in the sediments was significantly higher than phosphorous loading, with a distinct spatial difference; the total nitrogen content ranged from 127.2-2092.8 mg·kg -1 and total phosphorous content ranged from 222.1-528.4 mg·kg -1 . Moreover, nitrogen loading (1033.6 mg·kg -1 ) in the vegetated zones were higher than in the unvegetated zones (325.2 mg·kg -1 ). In addition, carbohydrate (3.7 mg·g -1 ) was the dominant component of sedimentary bioclastic material, with lipids (2.8 mg·g -1 ) being the second most abundant of the biodegradable compounds. The major sources of nutrients and biodegradable compounds in the sediment were massive aggregates of macrophyte detritus. The pigment, nutrient, and biodegradable compound contents in the vegetated zones were significantly higher than in unvegetated zones ( P <0.01). The benthic eutrophic state showed a trend from mesotrophic to eutrophic in Xukou Bay, which should be given more attention in the future management of freshwater lake ecosystems.

Progression through the cell cycle is driven by bistable switches-specialized molecular circuits that govern transitions from one cellular state to another. Although the mechanics of bistable switches are relatively well understood, it is less clear how cells integrate multiple sources of molecular information to engage these switches. Here, we describe how bistable switches act as hubs of information processing and examine how variability, competition, and inheritance of molecular signals determine the timing of the Rb-E2F bistable switch that controls cell cycle entry. Bistable switches confer both robustness and plasticity to cell cycle progression, ensuring that cell cycle events are performed completely and in the correct order, while still allowing flexibility to cope with ongoing stress and changing environmental conditions., (© 2019 Federation of European Biochemical Societies.)

Climatic oscillations during the last glacial maximum (LGM) significantly affected the distribution patterns and genetic structure of extant plants. Northeast China (NEC) is a major biodiversity center in East Asia, and the influence of historical climate change on NEC populations is critical for understanding species responses to future climate change. However, only a few phylogeographic studies of cool temperate deciduous tree species have been conducted in the area, and results are inconsistent for species with different niches or distribution areas. We employed multiple chloroplast and nuclear markers to investigate the genetic structure of two ecologically contrasting species, Betula platyphylla and B .  ermanii , in NEC. Rare haplotypes were identified in the chloroplast genome of these species, and both exhibited high levels of nucleotide diversity based on a fragment of the nuclear gene G3PDH and microsatellites. Moreover, significant phylogeographic structure was detected for B. platyphylla , suggesting that these populations had recolonized from independent glacial refuges, whereas no genetic structure was found for B .  ermanii ., Open Research Badges: The nSSR datasets used in the current study and the table of pairwise FST (below diagonal) and its standardized F'ST (above diagonal) among 25 populations based on seven SSRs are available from the Dryad (DOI: https://doi.org/10.5061/dryad.230d176). Sequences generated from this study were deposited in GenBank under Accession nos. KY199568-KY200162 and MK819541-MK819970., Competing Interests: The authors declare that they have no competing interests., (© 2019 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

In this study, the anti-inflammatory mechanisms of Quercetin (Que) on atopic dermatitis (AD)-like skin lesions was examined. The left ear of mice was applied with MC903, followed by Que. administration daily on the ear for 8 days. Then macroscopic and histologic examination was performed to detect the severity of skin lesions. In the skin section of AD mice, we observed that Que. could reduce the expression of CCL17, CCL22, IL-4, IL-6, IFN-γ and TNF-α. In vitro, the anti-inflammatory effects of Que. were examined on human keratinocytes (HaCaT cells) treated with IFN-γ/TNF-α. To unveil the lncRNAs' regulatory role on Que-activated anti-inflammatory function, the next-generation high-throughput sequencing was performed in HaCat cells with or without Que. treatment, which profiled the expression of lncRNAs and mRNAs, the results illustrated that lnc-C7orf30-2, a lncRNA expressed differentially, was correlated with IL-6 expression. Silencing of lnc-C7orf30-2 by RiboTM lncRNA Smart Silencer proved its role on IL-6 expression. Therefore, the results here demonstrated that topical administration of Que. plays a beneficial role in controlling AD symptoms, which may serve as potential candidate for AD treatment., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Glioblastoma (GBM) is one of the lethal tumors with poor prognosis. However, prognostic prediction approaches need to be further explored. Therefore, we developed an evaluation system that could be used for prognostic prediction of GBM patients. Published mRNA expression datasets from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and Chinese Glioma Genome Atlas (CGGA) were analyzed. Quantitative Realtime-PCR of signature genes and molecular aberrations of 178 Xiangya GBM patients were used for confirmation. Gene set enrichment analysis (GSEA) was performed for functional annotation. As a result, we established a 13-gene signature which named Combined Therapy Sensitivity Index (CTSI). Based on a cutoff point, we divided patients into high-risk group and low-risk group. Based on Kaplan-Meier analysis and multivariate Cox regression analysis, we found that patients in the high-risk group had a shorter overall survival time than patients in the low-risk group (p<0.001 in TCGA and CGGA datasets, p=0.047 in GSE4271 dataset, p=0.008 in Xiangya GBM cohort, HR: 1.65-3.42). By comparing the status of IDH mutation, TERT promoter mutation (TERTp-mut) and MGMT promoter methylation, CTSI was predictable in IDH wild-type (IDH-wt)/MGMT promoter unmethylated (MGMTp-unmeth) patients (p=0.037 in IDH-wt/TERTp-mut/MGMTp-unmeth subgroup, HR: 1.98; p=0.032 in IDH-wt/TERTp-wt/MGMTp-unmeth subgroup, HR: 2.09). Based on GESA, the Gene Ontology (GO) gene sets were enriched differently between CTSI high-risk and low-risk groups. Our results showed CTSI risk score can predict the prognosis of IDH-wt/MGMTp-unmeth GBM patients. Based on CTSI, combined with the status of IDH mutation, TERT promoter mutation and MGMT promoter methylation, a stepwise prognosis evaluation system which can provide precise prognosis prediction for GBM patients was established., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

BACKGROUND The aim of this study was to review the efficacy and safety of intra-articular (IA) viscosupplementation (VS) for hip osteoarthritis (OA). MATERIAL AND METHODS We searched Medline, Clinical Trial Register Center, EMBASE, and Cochrane databases for randomized controlled trials (RCTs) comparing VS with placebo injection for hip OA. We included suitable studies, assessed the quality of studies, and extracted data on pain reduction, function improvement at different time points, and safety profiles. The comparisons of pain and function outcome were performed by meta-analysis. RESULTS Five high-quality randomized controlled studies trials (RCTs) with 591 patients with hip OA were identified. Although several trials demonstrated a significant decline in pain in VS groups during follow-up compared to baseline, without severe adverse events, the pooled analysis did not show VS was superior to placebo at any time windows [7-14 days: standardized mean difference (SMD): -0.18; 95% CI, -0.47 to 0.10, p=0.21; 28-30 days: 0.02 (-0.15, 0.19), p=0.82; or at final visit: -0.14 (-0.46, 0.18), p=0.38]. Similar results were also observed in the combined data of functional results. CONCLUSIONS IA VS does not reduce pain or improve function significantly better than placebo in a short-term follow-up. The benefits and safety of VS should be further assessed by sufficiently-sized, methodologically sound studies with validated assessment of more clinically relevant end-points.

The influence of reward on behavior is one of the hottest research subjects in psychological research. Reward-induced motivation promotes the performance of the participants. In the field of emotional processing, the reward can influence the individual's processing of emotional information, but previous studies have not directly discussed the effect of reward on emotional regulation. The present study focused on whether emotional regulation ability would be improved under the reward condition. Experiment 1 and 2 investigated the effect of reward on negative emotional down-regulation and positive emotional up-regulation respectively. In experiment 1, monetary reward stimulation was introduced on the basis of the classic emotion regulation paradigm, and the subjects were asked to regulate their negative emotion under the condition of reward or non-reward, and evaluate their current affective state subsequently. Similar to experiment 1, experiment 2 required subjects to up-regulate positive emotions under the condition of reward or non-reward. The results of experiment 1 showed that under the reward condition, the negative emotional regulation effect was significantly higher than that under the non-reward condition (P < 0.05). Experiment 2 also showed that compared to non-reward condition, the positive emotion regulation effect was significantly increased under the reward condition (P < 0.05). These results suggested that compared to non-reward condition, participants can regulate their emotion better under the condition of the reward. It is worth noting that the results of Experiment 1 and 2 may be caused by the incentive motivation induced by monetary stimulus, or the positive emotion caused by positive value of money information. Therefore, we carried out experiment 3 and 4 to explore whether the positive emotions induced by money itself can influence the emotional regulation of individuals. In experiment 3, the money pictures were used to induce the positive emotions of subjects, and the subjects were asked to regulate their negative emotion after the presence of money pictures or non-monetary picture, and evaluate their current affective state subsequently. Similarly, experiment 4 required subjects to regulate their positive emotion after the presence of money pictures. The results of experiment 3 and 4 showed that there was no significant difference in the subjects' scores of emotional pleasantness after the presence of money pictures or non-monetary picture (P < 0.05). The results of experiment 3 and 4 excluded the possibility that the positive emotions induced by simple money stimulus pictures could improve individual's emotional regulation ability. To sum up, the improvement of individual's emotional regulation ability was indeed driven by reward motivation in this study, that is, the motivation induced by reward can effectively promote individual's emotional regulation ability.

Purpose: Lung cancer is the most common malignant tumor in the world, and its incidence and mortality are very high. This study focuses on the mechanism of non-small cell lung cancer to find new therapeutic targets., Methods: We used RT-PCR and Western blot to verify the linear relationship between E2F1 and IRF5 in normal lung tissue and lung cancer tissues. Secondly, we used overexpression and knock down E2F1 in cell lines to detect the expression of IRF5. The prime enzyme reporter plasmid verified that E2F1 binds to the core promoter region of IRF5; finally, CHIP experiments demonstrated that E2F1 binds directly to IRF5., Results: We verified that E2F1 and IRF5 are decreased in patient tissues, and there is a strong linear relationship between E2F1 and IRF5. Secondly, we used overexpression of E2F1 or E2F1 siRNA transfected into HCC827 cells and found that E2F1 positively regulates the activity of the IRF5 promoter and the mRNA level of IRF5. Finally, the results of a chromatin immunoprecipitation assay demonstrated that E2F1 bound to the promoter region of IRF5 in vitro. These results suggested that the E2F1 transcription factor is the primary determinant for activating the basal transcription of the IRF5., Conclusion: The transcription factor E2F1 positively regulates IRF5 in non-small cell lung cancer., Competing Interests: The authors report no conflicts of interest in this work., (© 2019 Feng et al.)

Microarray expression profiles of lncRNAs and mRNAs were investigated in HepG2 cells treated with 20 μg/ml ginsenoside Rh2 as well as in ginsenoside Rh2-untreated cells. Microarray analysis showed 618 upregulated lncRNAs and 161 downregulated lncRNAs in HepG2 cells treated with ginsenoside Rh2 compared with the control group. Moreover, three differentially expressed lncRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). This may be beneficial to patients as an anti-cancer treatment and potentially provide novel targets for HCC (hepatocellular carcinoma) therapy.

A new species of the genus Tipulodina Enderlein, 1912, Tipulodinabifurcata Xue & Men, sp. nov. (Guangxi, South China) is described and illustrated. A key to the known species in China is provided. The morphological description of the female internal reproductive system of the new species is provided, which represents the first description for this genus.

Liver necroinflammation is the indicator for treating patients with chronic hepatitis B (CHB) infection. However, there is no suitable non-invasive index for diagnosing liver necroinflammation. This study aimed to create a non-invasive index to predict liver necroinflammation in patients who lack clear-cut clinical inflammation parameters. Patients who were hepatitis B e antigen (HBeAg)-negative and underwent liver histological diagnosis, had a normal or minimally increased alanine aminotransferase (ALT) level were enrolled. Liver necroinflammation was defined as histological active index ≥4. A logistic regression model (LRM) was established based on the parameters independently associated with liver necroinflammation. Of all 550 patients, 36.73% had necroinflammation. In patients with an abnormal ALT level, the rate of necroinflammation was 52.49%. The area under the curve (AUC) of the ALT level for predicting necroinflammation was 0.655 (95% confidence interval [CI], 0.609-0.702), and that of the HBV DNA level ≥2000 IU/mL combined with an abnormal ALT level was 0.618. By using the LRM, the AUC improved to 0.769 (95% CI, 0.723-0.815) with a Youden index of 0.519 and diagnostic accuracy of 75.3%. The cutoff value ≥0.7 in the LRM had a specificity of 97.4% and positive predictive value of 85.0% for predicting necroinflammation. By using the cutoff value <0.15 in the LRM, the presence of necroinflammation could be excluded with a negative predictive value of 90.8%. This study indicated that the LRM can be used to effectively diagnose liver necroinflammation in HBeAg-negative patients with CHB who have normal or minimally elevated ALT levels., (© 2019 John Wiley & Sons Ltd.)

Hepatitis B surface antigen (HBsAg) loss is considered a functional cure in chronic hepatitis B (CHB). However, the durability of HBsAg loss after stopping treatment remains unknown. This study aimed to assess the sustained functional cure achieved by interferon therapy in hepatitis B envelope antigen (HBeAg)-negative CHB patients. In this prospective study, 176 HBeAg-negative CHB patients with functional cure were enrolled for 12 weeks of cessation treatment, and treatment information and baseline data were collected. Hepatitis B virus (HBV) biomarkers and clinical biochemical indicators were evaluated every 3 months; liver imaging examinations were performed every 3-6 months during the 48-week follow-up. The sustained functional cure was evaluated. After the 48-week follow-up, the sustained functional cure rate was 86.63%. The cumulative rates of HBsAg reversion and HBV DNA reversion were 12.79% and 2.33%, respectively. Consolidation treatment ≥ 12 weeks after HBsAg loss achieved a significantly higher rate of sustained functional cure and significantly lower rate of HBsAg reversion than consolidation treatment < 12 weeks (76.19% vs 90.00%, P = 0.022 and 23.81% vs 9.23%, P = 0.014, respectively). Patients with hepatitis B surface antibody (HBsAb) had higher rate of sustained functional cure than patients achieving HBsAg loss but without HBsAb (89.86% vs 73.53%, P = 0.012). Consolidation treatment ≥ 12 weeks (odds ratio [OR] 16.478; 95% confidence interval [CI], 2.135-127.151; P = 0.007) and high HBsAb levels (OR 8.312; 95% CI, 1.824-37.881; P = 0.006) were independent predictors of sustained functional cure. Results suggested that 12 weeks of consolidation therapy after HBsAg clearance and elevated HBsAb levels help to improve functional cure., (© 2019 John Wiley & Sons Ltd.)

Mildew resistance locus O ( Mlo ) gene was first found in barley as a powdery mildew susceptibility gene, and recessive mlo alleles confer durable resistance to barley powdery mildew. To identify candidate Mlo susceptibility genes in rubber tree, HbMlo12 was cloned from rubber tree clone CATAS7-33-97, which is susceptible to powdery mildew. Protein architecture analysis showed that HbMlo12 was a typical Mlo protein with seven transmembrane domains. Protein blast search in the Arabidopsis thaliana proteome database showed that HbMlo12 shared the highest similarity with AtMlo12, with 63% sequence identity. Furthermore, HbMlo12 together with the dicot powdery mildew susceptible Mlo proteins (including AtMlo2, AtMlo6, AtMlo12, tomato SlMlo1, pepper CaMlo2, pea PsMlo1, etc.) were grouped into clade V. Subcellular localization analysis in tobacco epidermal cells revealed that HbMlo12 was localized to the endoplasmic reticulum membrane. HbMlo12 was preferentially expressed in the flower and leaf of rubber tree. Moreover, its expression was significantly upregulated in response to powdery mildew inoculation. Application of exogenous ethephon caused a distinct increase in HbMlo12 expression. Additionally, HbMlo12 transcript was quickly induced by spraying salicylic acid and gibberellic acid and reached the maximum at 0.5 h after treatments. By contrast, HbMlo12 expression was downregulated by methyl jasmonate, abscisic acid, and drought stress treatments. There was no significant change in HbMlo12 expression after indole-3-acetic acid, H 2 O 2 , and wounding stimuli. Taken together, these results suggested that HbMlo12 might be a candidate Mlo gene conferring susceptibility to powdery mildew in rubber tree. The results of this study are vital in understanding Mlo gene evolution and developing new rubber tree varieties with powdery mildew resistance using reverse genetics.

The field of circular non-coding RNAs have been gradually attracted wide attention with the developments of high-throughput sequencing. In this review, we systematically summarize three driving models for circRNAs biogenesis: intron-pairing-driven, RNA binding protein-driven and lariat-driven. In addition, we also briefly introduce the current research methods of circRNAs, which include high-throughput library construction methods, identification through bioinformatics and common experimental verification. Here, we also systematically summarize the functions of circRNAs, including microRNA (miRNA) or protein sponges, regulating the alternative splicing (AS) and expression of host genes, and extensive translation. Finally, we provide a systematic characterization and the latest research progress of circRNAs, which provide a new perspective for further studies of circRNAs in plants.

Here, we prepared the first series of 3D hybrid iodoplumbates with novel porous frameworks of [Pb8I21]5- directed by transition metal complex (TMC) cationic dyes of [TM(2.2-bipy)3]2+. The microporous materials exhibit outstanding visible light-driven photoelectric properties due to the effective photosensitization of the TMC dyes. The coexistence of stronger face- and weaker corner-shared connecting manners affords the feasibility of tailoring the 3D framework into low-dimensional skeletons, which provide a new structural prototype to modify the semiconducting properties similar to those of classic perovskites.

Background: The oriental fruit fly Bactrocera dorsalis (Hendel), a widespread agricultural pest, has evolved resistance to many insecticides, including organophosphorus compounds. Glutathione S-transferases (GSTs) are involved in xenobiotic detoxification and insecticide resistance in many insects. However, the role of delta class GSTs in detoxifying malathion in B. dorsalis is unknown. Here, we evaluated the roles of two delta class GSTs in malathion detoxification in this species., Results: Two delta class GSTs genes, BdGSTd1 and BdGSTd10, were characterized in B. dorsalis. They were highly expressed in 5-day-old adults, as well as in midgut and Malpighian tubules. Upon malathion exposure, the two genes were upregulated by 2.63- and 2.85-fold, respectively. Injection of double-stranded RNA targeting BdGSTd1 or BdGSTd10 significantly reduced their mRNA levels in adults and also significantly increased adult susceptibility to malathion. The expression of these two GSTs in Escherichia coli helped the host to endure malathion stress at a concentration of 10 µg mL -1 according to a Cell Counting Kit-8 assay. High-performance liquid chromatography analyses indicated that malathion could be significantly depleted by the two delta GSTs. The role of BdGSTd10 in malathion sequestration was also discussed., Conclusion: BdGSTd1 and BdGSTd10 play important roles in the detoxification of malathion in B. dorsalis. © 2019 Society of Chemical Industry., (© 2019 Society of Chemical Industry.)

Imipenem is widely used for the treatment of children with serious infections. Currently, studies on the pharmacokinetics of imipenem in children with hematological malignancies are lacking. Given the significant impact of disease on pharmacokinetics and increased resistance, we aimed to conduct a population pharmacokinetic study of imipenem and optimize the dosage regimens for this vulnerable population. After children were treated with imipenem-cilastatin (IMP-CS), blood samples were collected from the children and the concentrations of imipenem were quantified using high-performance liquid chromatography with UV detection. Then, a population-level pharmacokinetic analysis was conducted using NONMEM software. Data were collected from 56 children (age range, 2.03 to 11.82 years) with hematological malignancies to conduct a population pharmacokinetic analysis. In this study, a two-compartment model that followed first-order elimination was found to be the most suitable. The parameters of current weight, age, and creatinine elimination rate were significant covariates that influenced imipenem pharmacokinetics. As a result, 41.4%, 56.1%, and 67.1% of the children reached the pharmacodynamic target (the percentage of the time during the total dosing interval that the free drug concentration remains above the MIC of 70%) against sensitive pathogens with an MIC of 0.5 mg/liter with imipenem at 15, 20, and 25 mg/kg of body weight every 6 h (q6h), respectively. However, only 11.1% of the children achieved the pharmacodynamic target against Pseudomonas aeruginosa isolates with an MIC of 2 mg/liter at a dose of 25 mg/kg q6h. The population pharmacokinetics of imipenem were assessed in children. The current dosage regimens of imipenem result in underdosing against resistant pathogens, including Pseudomonas aeruginosa and Acinetobacter baumannii However, for sensitive pathogens, imipenem has an acceptable pharmacodynamic target rate at a dosage of 25 mg/kg q6h. (The study discussed in this paper has been registered at ClinicalTrials.gov under identifier NCT03113344.)., (Copyright © 2019 American Society for Microbiology.)

Objective:  To investigate the expression of brain-derived neurotrophic factor(BDNF) and tyrosine kinase B (TrkB) protein in the hippocampus of model rats of comorbid epilepsy and depression., Methods: A rat model of epilepsy was established using lithium chloride.pilocarpine. Among these epileptic rats, those with comorbid depression were selected by a battery of behavioral tests starting on the 14th day after establishing the epilepsy model. A depression group was established by unpredicted chronic mild stress (UCMS) and separate housing. These treatment groups were compared to an untreated control group. Thirteen rats per group were examined by immunofluorescence staining with optical density quantitation to determine the distribution of BDNF- and TrkB-positive cells in the hippocampus and by western blotting to estimate total protein expression levels during the 4th week after establishing the models. Immunofluorescence staining for NeuN was also conducted in hippocampus to evaluate neuronal survival. Depression-like behaviors were also assessed., Results:  Compared to the untreated control group and the epilepsy alone group, the comorbid group exhibited lower average optical densities of BDNF- and TrkB-immunopositive cells as well as lower total BDNF and TrkB protein expression levels (all P = 0.000). The comorbid group exhibited lower behavioral scores compared to all other groups (all P=0.000). Numbers of NeuN-positive cells were lower in the hippocampus of all three experimental groups compared to the untreated control group (all P = 0.000)., Conclusions:  These results suggest that hypofunctional BDNF-TrkB signaling may contribute to depression in epilepsy., Abbreviations: BDNF: Brain-derived neurotrophic factor; TrkB: tyrosine kinase B; UCMS: unpredicted chronic mild stress; PBS: phosphate-buffered saline; HS: Hippocampal sclerosis.

Microglia activation-mediated neuroinflammation plays an important role in the progression of Parkinson's disease (PD). However, effects of microglia activation on dopaminergic neuronal cell (DAC) fate are still poorly understood. The objective of this study was to explore the neurotoxic effects of microglia activation-mediated oxidative injury in DACs and its possible mechanisms. In the present study, microglia-DACs co-culture systems (murine BV-2 and MN9D cells, or primary microglia and mesencephalic neurons) were used to display the crosstalk between both cell types. The cytotoxicity of lipopolysaccharide-induced microglia activation led to the accumulation of intracellular reactive oxygen species, increased cell apoptosis rate, reduced number of DACs, concomitant to cell cycle arrest at G 1 phase. Molecular mechanisms of apoptosis caused by microglia activation-induced oxidative injury included the increased opening of mitochondrial permeability transition pore and enhanced membrane potential depolarization in MN9D cells, down-regulation of Bcl-2 and up-regulation of Bax, caspase-3 expression in DACs. In addition, microglia activation made a significant reduction of SIRT3 and superoxide dismutase 2 gene expression in DACs. Taken together, these data imply that microglia activation promotes cell apoptosis through mitochondrial pathway and decreases SIRT3 expression in DACs, which may provide some support for PD progression promoted by neuroinflammation.

Our previous studies demonstrated that prenatal caffeine exposure (PCE) caused thymopoiesis inhibition, immune disorders, and airway remodeling in offspring, which raises the question of whether PCE is a risk factor for postnatal asthma. Meanwhile, the mechanism of PCE-induced thymopoiesis inhibition is not clear yet. Considering caffeine's pro-autophagy effects (lacking evidence in thymus) and the important role of autophagy in maintaining thymopoiesis, this study aimed to investigate whether PCE contributes to asthma susceptibility, and further explore the molecular mechanisms of thymopoiesis inhibition from the perspective of pro-autophagy effects of caffeine both in vivo and in vitro. The PCE mouse model was established by 96 mg/kg/day caffeine administration from gestational day (GD) 9-GD 18, and an asthma model was established on the offspring by ovalbumin sensitization and challenge. The results confirmed our hypothesis that PCE could suppress pulmonary CD4 + T development and aggravate allergen-induced asthma symptoms in the offspring. In fetuses, PCE significantly suppressed A2AR-PKA signaling, upregulated Beclin1-LC3II autophagy, promoted Bcl10 degradation, reduced A20 expression, and inhibited CD4 + T thymopoiesis. Similar results were also observed in 4 µM caffeine-treated thymocytes in vitro. Moreover, inhibiting A2AR by antagonist (SCH 58261) performed the same downstream biological effects as caffeine treatment, and autophagy inhibitor (BafilomycinA1) clearly abolished the caffeine-induced Bcl10 degradation and A20 suppression. In conclusion, our findings, for the first time, showed that PCE could attenuate CD4 + T thymopoiesis and suppress pulmonary CD4 + T development by directly enhancing autophagy in thymocytes, and provided a firm experimental evidence that PCE is a risk factor for postnatal asthma.

Clinical study showed that smoking during pregnancy deceased the thymus size in newborns. However, the long-term effect remains unclear. This study was aimed to observe the effects of prenatal nicotine exposure (PNE) on the development of thymus and the T-lymphocyte subpopulation in mice offspring from the neonatal to adulthood. Both the thymus weight and cytometry data indicated that PNE caused persistent thymic hypoplasia in male offspring from neonatal to adult period and transient changes in female offspring from neonatal to prepuberal period. Flow cytometry analysis disclosed a permanent decreased proportion and number of mature CD4 single-positive (SP) T cells in thymus of both sex. In addition, the PNE male offspring showed a more serious thymus atrophy in the ovalbumin (OVA)-sensitized model. Moreover, increased autophagic vacuole and elevated mRNA expression of Beclin 1 were noted in PNE fetal thymus. In conclusion, PNE offspring showed thymus atrophy and CD 4 SP T cell reduction at different life stages. Mechanically, PNE induced excessive autophagy in fetal thymocytes might be involved in these changes. All the results provided evidence for elucidating the PNE-induced programmed immune diseases., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The cell cycle is canonically described as a series of four consecutive phases: G1, S, G2, and M. In single cells, the duration of each phase varies, but the quantitative laws that govern phase durations are not well understood. Using time-lapse microscopy, we found that each phase duration follows an Erlang distribution and is statistically independent from other phases. We challenged this observation by perturbing phase durations through oncogene activation, inhibition of DNA synthesis, reduced temperature, and DNA damage. Despite large changes in durations in cell populations, phase durations remained uncoupled in individual cells. These results suggested that the independence of phase durations may arise from a large number of molecular factors that each exerts a minor influence on the rate of cell cycle progression. We tested this model by experimentally forcing phase coupling through inhibition of cyclin-dependent kinase 2 (CDK2) or overexpression of cyclin D. Our work provides an explanation for the historical observation that phase durations are both inherited and independent and suggests how cell cycle progression may be altered in disease states., (© 2019 The Authors. Published under the terms of the CC BY 4.0 license.)

Elucidating the mechanisms underlying the genetic divergence between closely related species is crucial to understanding the origin and evolution of biodiversity. The genus Aquilegia L. has undergone rapid adaptive radiation, generating about 70 well-recognized species that are specialized to distinct habitats and pollinators. In this study, to address the underlying evolutionary mechanisms that drive the genetic divergence, we analyzed the whole genomes of two ecologically isolated Aquilegia species, A. oxysepala and A. japonica as well as their putative hybrid. Our comparative genomic analyses reveal that while the two species diverged only recently and experienced recurrent gene flow, a high level of genetic divergence is observed in their nuclear genomes. In particular, candidate genomic regions that show signature of selection differ dramatically between the two species. Given that the splitting time of the two species is broadly matched with the decrease in effective population sizes, we propose that allopatric isolation together with natural selection have preceded the interspecific gene flow in the process of speciation. The observed high genetic divergence is likely an outcome of combined effects of natural selection, genetic drift and divergent sorting of ancestral polymorphisms. Our study provides a genome-wide view of how genetic divergence has evolved between closely related species., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Toxoplasma gondii is one of the most widespread obligatory parasitic protozoa and infects nearly all warm-blooded animals, leading to toxoplasmosis. The therapeutic drugs currently administered, like the combination of pyrimethamine and sulfadiazine, show high rates of toxic side effects, and drug resistance is encountered in some cases. Resveratrol is a natural plant extract with multiple functions, such as antibacterial, anticancer, and antiparasite activities. In this study, we evaluated the inhibitory effects of resveratrol on tachyzoites of the Toxoplasma gondii RH strain extracellularly and intracellularly. We demonstrate that resveratrol possesses direct antitoxoplasma activity by reducing the population of extracellularly grown tachyzoites, probably by disturbing the redox homeostasis of the parasites. Moreover, resveratrol was also able to release the burden of cellular stress, promote apoptosis, and maintain the autophagic status of macrophages, which turned out to be regulated by intracellular parasites, thereby functioning indirectly in eliminating T. gondii In conclusion, resveratrol has both direct and indirect antitoxoplasma effects against RH tachyzoites and may possess the potential to be further evaluated and employed for toxoplasmosis treatment., (Copyright © 2019 American Society for Microbiology.)

Objective: To compare computer measurement semi automatic quantitative detection software system with ultra thin layer pathological section to confirm the avascular necrosis percentage of the femoral head, and provide reference for clinical treatment options., Methods: From June 2012 to December 2013, the X-ray and MRI of 24 patients(24 hips on unilateral) were reviewed, who had avascular necrosis of the femoral head at late stage (stage III and IV) according to the ARCO international staging system, and performed by total hip arthroplasty. There were 15 males and 9 females, with an average age of (65.1±8.8) years old ranging 33 to 74 years old. Based on imaging system combined with computer aided technology(CAD) system and postoperative ultrathin slice, the volume of the area of femoral head necrosis were calculated. Then combining with the total volume of the femoral head was calculated by X-ray, the percentage of each femoral head necrosis area was calculated as a percentage of the whole ball head in both methods., Results: For 24 hips, the normal femoral head volume was (39.58±3.29) cm³ on average of X-ray film, the necrotic volume was (20.00±3.04) cm³ on average of MRI by the calculation of computer. The necrotic volume occupying in the volume of the normal femoral head was (42.92±6.09)% on average ranged. The necrotic lesion size was larger than 40% in 16 hips, 30% to 40% in 8 hips, 1 ess than 30% in 0 hip. Under the pathological section, the necrosis volume was (19.89±3.17) cm³, the necrotic volume occupying in the volume of the normal femoral head was (40.33±6.36)%. The necrotic lesion size was larger than 40% in 12 hips, 30% to 40% in 11 hips, 1 ess than 30% in 1 hip. In computer and general measurement, the two entire femoral head volume difference was (0.113±0.466) cm³, there was no significant difference using these measurements( t =-1.186, P =0.248). After the linear correlation statistics analysis, there was a positive correlation relationship in necrotic volume between computer software and pathology measurement(γ=0.980, P =0.000)., Conclusions: The severity of the necrotic femoral head is closely related to the percentage of necrotic area. When the ratio of necrotic lesions and the whole femoral head is greater than 30%, the patients' clinical symptoms tend to aggravate, the probability of total hip arthroplasty increased significantly. It have great significances in femoral head necrosis installment, judge the prognosis, guide the selection of treatment and monitoring curative effect., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© 2019 by the China Journal of Orthopaedics and Traumatology Press.)

Thoracic outlet syndrome(TOS) are constellation of symptoms caused by compression of the neurovascular bundle including the brachial plexus, the subclavian artery and the subclavian vein at the thoracic outlet region. It includes neurogenic TOS, venus TOS, arterial TOS, and neurogenic TOS is the most common type. TOS has varied manifestations and lack of confirmatory testing, therefore, the diagnosis should be conbination with thorough history, physical examination and associated supplementary examinations. Conservative and surgical treatment can be choosed for TOS and the outcomes are generally good. Conservative management is the initial treatment strategy for neurogenic TOS. In cases of symptomatic vascular TOS and neurovascular TOS, which has been failed by conservative treatment, surgery should be considered more promptly., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© 2019 by the China Journal of Orthopaedics and Traumatology Press.)

Paraquat (PQ) intoxication causes thousands of mortalities every year, worldwide. Its pulmonary-targeted accumulation and the acute lung injury it subsequently causes, remain a challenge for detoxification treatment. A previous study has demonstrated that the upregulation of nuclear factor erythroid-2 related factor 2 (Nrf2) prevents PQ toxicity in cell line and murine models. As Nrf2 target genes include a group of membrane transporters, the current study assessed the protective mechanism exerted by Nrf2 against PQ toxicity and intracellular PQ accumulation via its effects on P-glycoprotein (P-gp), a downstream transporter of Nrf2. Adenovirus vectors containing the Nrf2 gene were transfected into A549 cells. Cell proliferation was assessed by Cell Counting Kit-8. The levels of LDH, MDA, SOD, TNF-α, IL-6 levels were detected using their respective ELISA kits. In addition, the levels of Nrf2 and P-gp protein expression were detected by western blot analysis. The concentration of PQ was measured by HPLC. The results revealed that overexpressed Nrf2 significantly increased P-gp protein levels, decreased the intracellular accumulation of PQ and attenuated PQ-induced toxicity. However, the protective effects of Nrf2 overexpression on PQ-challenged A549 cells were abrogated following cyclosporine A treatment, a competitive inhibitor of P-gp, which also increased intracellular PQ levels. These data indicated that Nrf2 gene overexpression prevented PQ toxicity in A549 cells, potentially via the upregulation of P-gp activity and the inhibition of intracellular PQ accumulation. Thus, Nrf2 and P-gp may serve as potential therapeutic targets for the treatment of PQ-induced injury.

Numerous studies had investigated the biological basis of spleen deficiency syndrome on gastrointestinal dysfunctions. However, little was known about neuropsychological mechanism of spleen deficiency syndrome. The default model network (DMN) plays an important role in cognitive processing. Our aim is to investigate the change of neuropsychological tests and DMN in patients with spleen deficiency syndrome.Sixteen patients and 12 healthy subjects underwent functional magnetic resonance imaging examination, and 15 patients with spleen deficiency syndrome and 6 healthy subjects take part in the two neuropsychological tests.Compared with healthy subjects, patients with spleen deficiency syndrome revealed significantly increased functional connectivity within DMN, and significantly higher in the scores of 2-FT (P = .002) and 3-FT (P = .014).Our findings suggest that patients with spleen deficiency syndrome are associated with abnormal functional connectivity of DMN and part of neuropsychological tests, which provide new evidence in neuroimaging to support the notion of TCM that the spleen stores Yi and domains thoughts.

Non-small cell lung cancer (NSCLC) is one of the most common malignancies, and Taxol is a cornerstone in the treatment. However, taxol-resistance eventually limits the clinical effects and applications. Daurinoline could restore the sensitivity of resistant MCF-7/adr and KBv200 cells. Whereas, the effect of daurinoline on the chemo-resistant NSCLC cells and the mechanism has not been elucidated. In this study, daurinoline was firstly demonstrated that inhibited the proliferation, migration, invasion and EMT phenotype of chemo-resistant NSCLC cells. And these effects were associated with EMT and Notch-1 reversal. Moreover, daurinoline could significantly enhance the anti-tumor effect of Taxol rather than epirubicin, adriamycin and cisplatin. And the reverse fold (RF) value of daurinoline was greater than terfenadine reported before. There are little cytotoxic effects of daurinoline and its derivatives reported by L.W. Fu, et al. (2001). Therefore, daurinoline may be a potential anti-tumor agent or chemosensitizer for chemo-resistant NSCLC patients., (Copyright © 2018. Published by Elsevier B.V.)

Human neuroglobin (Ngb) forms an intramolecular disulfide bond between Cys46 and Cys55, with a third Cys120 near the protein surface, which is a promising protein model for heme protein design. In order to protect the free Cys120 and to enhance the protein stability, we herein developed a strategy by designing an additional disulfide bond between Cys120 and Cys15 via A15C mutation. The design was supported by molecular modeling, and the formation of Cys15-Cys120 disulfide bond was confirmed experimentally by ESI-MS analysis. Molecular modeling, UV-Vis and CD spectroscopy showed that the additional disulfide bond caused minimal structural alterations of Ngb. Meanwhile, the disulfide bond of Cys15-Cys120 was found to enhance both Gdn·HCl-induced unfolding stability (increased by ∼0.64 M) and pH-induced unfolding stability (decreased by ∼0.69 pH unit), as compared to those of WT Ngb with a single native disulfide bond of Cys46-Cys55. Moreover, the half denaturation temperature ( T m ) of A15C Ngb was determined to be higher than 100 °C. In addition, the disulfide bond of Cys15-Cys120 has slight effects on protein function, such as an increase in the rate of O 2 release by ∼1.4-fold. This study not only suggests a crucial role of the artificial disulfide in protein stabilization, but also lays the groundwork for further investigation of the structure and function of Ngb, as well as for the design of other functional heme proteins, based on the scaffold of A15C Ngb with an enhanced stability., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Hyperthermia has been clinically utilized as an adjuvant therapy in the treatment of cervical carcinoma. However, thermotolerance induced by heme oxygenase-1 (HO-1), a stress-inducible cytoprotective protein, limits the efficacy of hyperthermic therapy, for which the exact mechanism remains unknown. In the present study, we found that heat treatment induced HO-1 expression and decreased copy number of HPV16 in cervical cancer cells and tissues from cervical cancer and precursor lesions. Knockdown of HO-1 stimulated autophagy accompanied by downregulation of X-linked inhibitor of apoptosis protein. Furthermore, silencing of HO-1 led to cell intolerance to hyperthermia, as manifested by inhibition of cell viability and induction of autophagic apoptosis. Moreover, HO-1 modulated hyperthermia-induced, autophagy-dependent antiviral effect. Thus, the findings indicate that blockade of HO-1 enhances hyperthermia-induced autophagy, an event resulting in apoptosis of cervical cancer cells through an antiviral mechanism. These observations imply the potential clinical utility of hyperthermia in combination with HO-1 inhibition in the treatment of cervical cancer., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Rabbit is susceptible to intestinal infection, which often results in severe inflammatory response. To investigate whether the special community structure of rabbit intestinal bacteria contributes to this susceptibility, we compared the inflammatory responses of isolated rabbit crypt and villus to heat-treated total bacteria in pig, chicken, and rabbit ileal contents. The dominant phylum in pig and chicken ileum was Firmicutes, while Bacteroidetes was dominant in rabbit ileum. The intestinal bacteria from rabbit induced higher expression of toll-like receptor 4 (TLR4) in rabbit crypt and villus (P < 0.05). TLR2 and TLR3 expression was obviously stimulated by chicken and pig intestinal bacteria (P < 0.05) but not by those of rabbit. The ileal bacteria from those three animals all increased the expression of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) in crypts and villus (P < 0.05). Chicken and pig ileal bacteria also stimulated the expression of anti-inflammatory factors interferon beta (IFN-β) and IL-10 (P < 0.05), while those of rabbit did not (P > 0.05). In conclusion, a higher abundance of Gram-negative bacteria in rabbit ileum did not lead to more expressive pro-inflammatory cytokines in isolated rabbit crypt and villus, but a higher percentage of Lactobacillus in chicken ileum might result in more expressive anti-inflammatory factors.

Background: Tanshinone IIA (Tan IIA) and Omentin-1 have a protective role in the cardiovascular system. However, if and how Tan IIA and Omentin-1 regulate cholesterol metabolism in macrophages has not been fully elucidated., Objective: To investigate the possible mechanisms of Tan IIA and Omentin-1 on preventing macrophage cholesterol accumulation and atherosclerosis development., Methods: The effect of Tan IIA on the protein and mRNA levels of Omentin-1 and ATP-binding cassette transporter A1 (ABCA1) in macrophages was examined by Western blot and qRT-PCR assay, respectively. Cholesterol efflux was assessed by liquid scintillation counting (LSC). Cellular lipid droplet was measured by Oil Red O staining, and intracellular lipid content was detected by high performance liquid chromatography (HPLC). In addition, the serum lipid profile of apoE-/- mice was measured by enzymatic method. The size of atherosclerotic lesion areas and content of lipids and collagen in the aortic of apoE-/- mice were examined by Sudan IV, Oil-red O, and Masson staining, respectively., Results: Tan IIA up-regulated expression of Omentin-1 and ABCA1 in THP-1 macrophages, promoting ABCA1-mediated cholesterol efflux and consequently decreasing cellular lipid content. Consistently, Tan IIA increased reverse cholesterol transport in apoE-/- mice. Plasma levels of high-density lipoprotein cholesterol (HDL-C), ABCA1 expression and atherosclerotic plaque collagen content were increased while plasma levels of low-density lipoprotein cholesterol (LDL-C) and atherosclerotic plaque sizes were reduced in Tan IIA-treated apoE-/- mice. These beneficial effects were, however, essentially blocked by knockdown of Omentin-1., Conclusion: Our results revealed that Tan IIA promotes cholesterol efflux and ameliorates lipid accumulation in macrophages most likely via the Omentin-1/ABCA1 pathway, reducing the development of aortic atherosclerosis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)